Method for testing the interaction between at least one liquid sample and respective solid sample

ABSTRACT

The invention relates to a method for testing the interaction between at least one liquid sample and a respective solid sample. The method comprises at least the steps of—providing adjacent first and second cavities, where said first and second cavities are in mutual communication via at least one passage, —placing the solid sample in said first cavity, —introducing the liquid sample in one of said first and second cavities, —sealing at least said first and second cavities from the exterior, so as to form a closed system of communicating cavities, —bringing said liquid sample into contact with the solid sample in said first cavity, transferring substantially all of said liquid sample to the second cavity after it has been brought into contact with the solid sample, —and testing the desired properties of any one or both of said liquid sample or said solid sample.

The present invention relates to a method for testing the interactionbetween at least one liquid sample and a respective solid sample.

In the field of microbiologically derived products, such as e.g.enzymes, there is a pronounced demand for test methods with a greatthroughput, i.e. for testing the microbiologically derived products froma lot of different microbes for a desired effect. An example of suchtesting could be the testing of the abovementioned enzymes for theircleaning abilities.

Presently, when testing such microbiologically derived products in theform of enzymes, the enzymes are contained in open containers. Theenzymes in the containers are in a liquid phase, which may be the liquidmedium in which the microbes were grown, preferably but not necessarilyafter the microbes have been filtered out. During the testing, a solidsample carrying a contamination suitable for the testing is gripped byappropriate means, immersed into the liquid, stirred to simulate acleaning process, and retracted from the liquid for optical inspection.

This method has the disadvantage that the gripping means has to becleaned after each test of a liquid sample in order to avoidcontamination of the succeeding liquid sample.

The method furthermore has the disadvantage that the retracted solidsample is taken away from the liquid in the container for inspection.This entails that it is at best difficult to track and recover a liquidsample which shows the desired cleaning effect, or at worst impossible,as the open containers cannot be stored appropriately. This thencomplicates subsequent detailed testing of the enzyme or further growthof the microbe.

It is the object of the present invention to provide a method and adevice, which overcomes the above disadvantages.

According to the present invention this problem is solved by a methodaccording to the opening paragraph wherein said method comprises atleast the steps of providing adjacent first and second cavities, wheresaid first and second cavities are in mutual communication via at leastone passage, placing the solid sample in said first cavity, introducingthe liquid sample in one of said first and second cavities, sealing atleast said first and second cavities from the exterior, so as to form aclosed system of communicating cavities, bringing said liquid sampleinto contact, with the solid sample in said first cavity, transferringsubstantially all of said liquid sample to the second cavity after ithas been brought into contact with the solid sample, and testing thedesired properties of any one or both of said liquid sample or saidsolid sample.

By the method according to the invention the rate with which the samplescan be tested is substantially increased because no separate grippingand handling means for the solid samples is needed during neither thesimulation of the cleaning process nor the subsequent testing. Moreoverthis removes the need to clean the gripping and handling means betweenseparate respective samples, because both the simulated cleaning processand testing can be preformed without removing the liquid and solidsamples from the cavities of the closed system.

In a preferred embodiment of the method said liquid sample is repeatedlytransferred between said first and second cavity, so as to enhance theinteraction between said liquid sample and said solid sample.

In a further preferred embodiment of the method a plurality of closedsystems of first and second cavities are provided.

Providing a plurality of closed systems is advantageous as it allows forsimultaneous execution of the aforementioned steps for several liquidand solid samples.

In another preferred embodiment of the method said testing is performedwithout breaking the sealing of said closed system.

This is advantageous in that it is thus not necessary to have grippingand handling means for this step thereby obviating the need for any timeconsuming cleaning thereof. Rather, the testing may be preformedcontinuously as the liquid and solid samples pass by a testing station.

In a particularly preferred embodiment of the method said testingcomprises optical inspection of said solid sample in said first cavityafter the transfer of substantially all of said liquid sample to saidsecond cavity.

Optical inspection is advantageous in that it is a simple way ofevaluating the cleaning properties of enzymes.

In yet another preferred embodiment of the method the mutualcommunication between said first and said second cavity is interruptedafter said transfer of substantially all of said liquid sample to saidsecond cavity, so as to seal said first and second cavities from eachother.

In this way the tested solid and in particular liquid samples mayconveniently be stored in the respective cavities for further detailedtesting or examination if the optical inspection indicates that themicrobiologically derived product in the sample exhibits the desiredproperties.

In an implementation of the method liquid is transferred between saidcavities by means of rollers.

This is advantageous when a large number of systems of interconnectedfirst and second cavities are arranged side by side in a continuous webin such a manner that the at each system of first and second cavitiesand the passage, lie in the longitudinal direction of the web. Thereby,as the web is moved in a continuous manner, the roller will first pressthe liquid from the first cavity to the second when the first cavitypasses the roller and subsequently press the liquid back to the firstcavity when the second cavity passes the roller. Using a number ofstaggered rollers is in that case a convenient means for achieving thatsaid liquid sample is repeatedly transferred between said first andsecond cavity as mentioned above.

In another preferred embodiment of the method the first and secondcavities and the at least one passage are repeatedly manufactured asrecesses in a first continuous web of flexible foil which aresubsequently covered and sealed by a second continuous web of flexiblefoil.

By forming the first and second cavities in a continuous web, acontinuous process may be achieved, where the cavities are manufacturedfrom a foil, filled, sealed, influenced by e.g. rollers, and inspected.

Preferably said first continuous web is of a thermoplastic material.Using a thermoplastic material will allow for simple manufacture of thecavities, by a suitable process such a thermoforming. Moreover the useof a thermoplastic material is a convenient way of providing all thedesired properties to the cavities, such as flexibility, transparency,liquid proof containing of the samples, etc.

Preferably, also said second continuous web of the same material as thefirst continuous web. This allows e.g. for easy sealing of the cavitiesby joining the first and second webs by welding, which is in turnadvantageous in that it dogs not entail the risk of contamination of thesamples with e.g. glue.

In another preferred embodiment the closed system of first and secondcavities comprise at least one further cavity.

Such a configuration would, depending on the samples to be tested, beadvantageous, e.g. in a system where it is necessary to apply a rinsingliquid to the solid sample after the interaction between the liquidsample and the solid sample.

The invention will now be described in greater detail by means of anon-limiting exemplary embodiment and with reference to the figures onwhich,

FIG. 1 is a schematic illustration of an apparatus for carrying out themethod according to the invention,

FIG. 2 a is a schematic illustration of the sealing of theinterconnected cavities according to one configuration of the cavities,

FIG. 2 b is a schematic illustration of the sealed interconnectedcavities according to an alternative configuration of the cavities,

FIG. 3 a to 3 d are schematic drawings illustrating the interactionbetween the rollers and the cavities, and

FIG. 4 is a schematic illustration of various configurations of theinterconnected cavities.

In FIG. 1 is illustrated an apparatus for carrying out the methodaccording to the invention. The apparatus is adapted for continuousoperation. Reference numeral 1 depicts a roll of a web material in theform of a transparent plastic foil 2. The transparent foil 2 is unrolledfrom the roll 1 in the direction of the arrow D in FIG. 1 by appropriateconveyor means, which include a first roller 3. The first roller 3 notonly serves as conveyor means but also for forming a number of cavities4. These may e.g. be formed permanently by an appropriate method such asthermoforming of the transparent foil 2. Alternatively they may beformed in a temporary fashion by suction of the foil 2 into appropriatedies (not shown) in which the foil is held by sustained suction untilthe cavities 4 are sealed, as will be described further below. Thesedies may be provided in a conveyor belt 5 running around the firstroller 3 and a second roller 6.

After the cavities 4 have been formed, be it permanently or temporarily,the transparent plastic, foil 2 is conveyed past a first filing station7. At this first filling station a liquid sample 9, seen only in FIGS. 2and 3, is introduced in some of the cavities, e.g. every other in thedirection across the web as illustrated in FIG. 2 b, or every other inthe direction D, as illustrated in FIG. 2 a. It should be noted that thedrawings is schematic and that the introduction may be performed in anyknown manner e.g. by means of a plurality of pipettes (not shown)extracting the liquid samples 9 from an array of open containers 14. Theliquid sample 9 may evidently also be introduced in all of the cavities,or be allowed to distribute itself in these as illustrated in FIG. 3 a.Further, an identification marking such as a bar code identifying theliquid sample 9 may be printed on the foil in the vicinity of eachfilled cavity 4.

Following the first filling station 7 is a second filling station 8 pastwhich the transparent foil 2 is conveyed. At this second filling stationa solid samples 10 are introduced in some of the cavities. Preferablythe solid samples 10 are introduced into the remaining cavities 4, notfilled with the liquid sample. Alternatively, however, the solid samples10 could be introduced in the same cavities as the liquid sample 8, andthe remainder of the cavities 4 be left empty. It should be noted, thateven though the following description and the claims refer to solidsamples and the interaction of the liquid sample 9 therewith, it is tobe understood that the solid samples 10 may merely act as carriers for asuitable contamination, or that the contamination is itself a solidprovides on an also solid carrier. What is in either case then tested isthe interaction between the liquid samples 9 and the contamination ofthe solid samples 10.

After the cavities 4 have been filled with liquid samples 9 and solidsamples 10 in a desired fashion, the cavities 4 are sealed.

For the sealing a second transparent foil 11 is used. Instead of beingtransparent, this second foil 11 may be opaque or translucent having anyappropriate background colour appropriate for subsequent opticalinspection of the solid samples 10 and/or the liquid samples 9. Itshould be noticed, that if the first foil 2 and the second foil 11 arenot both transparent, it is evidently of no importance whether it is thefirst foil 2 or the second foil 11, which has the background colour.Thus in this case the first foil 2 could instead be the opaque ortranslucent one with the appropriate background colour appropriate forsubsequent optical inspection.

The second foil 11 is unwound from a roll 12. It is brought into contactwith the first foil 2 by means of a roller 13. The sealing is preferablycarried out by means of welding, because it minimises the risk ofpolluting the samples in the cavities 4, e.g. as compared to the risk ofglue residues from gluing. Gluing is however not excluded. The weldingmay be any appropriate welding method, such as laser welding, ultrasonicwelding, or welding by means of direct application of heat, e.g. fromthe roller 13. The cavities 4 are not yet individually sealed at thisstage. Rather, the cavities 4 are sealed from the exterior, so as toform small systems. Within these systems passages 15 left unsealed. Suchunsealed passages 15 may be provided in a plurality of different waysdepending on the sealing method. If, as preferred, heat welding by meansof the roller 13 is used, corresponding channels could be provided inthe thermoforming die, thereby ensuring that desired parts of the firstfoil 2 are not brought into contact with the second foil 11 by theroller 13 during the welding.

FIG. 4 illustrates various configurations of the cavities 4 within thesealed systems. The sealed systems comprise at least two interconnectedcavities 4, i.e. a first and a second cavity. As can be seen from FIG.4, this system of a first and a second cavity sealed off from theexterior, may comprise further cavities. Such a configuration would,depending on the samples to be tested, be advantageous, e.g. in a systemwhere it is necessary to apply a rinsing liquid to the solid sample 10after the interaction between the liquid sample 9 and the solid sample.

After the cavities 4 have been sealed, they are passed under a number ofrollers 16, 17 and 18 serving to displace the liquid sample 9 betweenthe cavities 4. Only three rollers 16, 17 and 18 are shown in FIG. 1,but a different number of rollers may equally be used.

Each of the rollers 16, 17 and 18 have a profiled surface, with raisedportions and recesses. In an alternative embodiment the rollers may besubstituted by a number of spaced disks. The location of the raisedportions and the recesses are staggered across the web from one rollerto the next.

These rollers serve to displace the liquid sample 9 between the cavities4 of the sealed. Systems, as will be explained below with reference toFIGS. 3 a to 3 d.

FIG. 3 a to 3 d illustrate a cross section of the cavities 4corresponding various situations that occur along the apparatus ofFIG. 1. Thus, FIG. 3 a illustrate the cross section of the cavities 4,as it will appear between the sealing of the cavities 4 at roller 13 andthe first roller 16 in FIG. 1.

When the web with the cavities 4 is conveyed along the apparatus, theypass under the first roller 16, as illustrated in FIG. 3 b. The firstroller 16 is profiled so as to have recesses and raised parts. Theraised parts are arranged so as to be aligned with every other of thecavities 4 across the web. The roller 16 thus engages only some of thecavities 4. When the roller 16 engages the cavities 4 the liquid sampleis pressed via the passage 15 into the neighbouring cavity 4 in whichthe solid sample 10 is located.

After having passed the first roller 16 the cavities 4 may, depending onthe elastic properties of the first foil 2 and the second foil 11,return to the situation illustrated in FIG. 3 a. Alternatively theliquid sample 9 remains in the cavity 4 together with the solid sample10 until the cavities reach the second roller 17, as illustrated in FIG.3 c. The second roller 17 is also profiled so as to present raisedparts. The raised parts are, however, staggered with respect to those ofthe first roller 16. Thus, when the web passes under the second roller17 the liquid sample is pressed back into the empty cavity 4, i.e. thecavity 4 without the solid sample 10. This process may be repeated byhaving several sets of rollers 16 and 17 arranged in an alternatingmanner after each other along the apparatus of FIG. 1.

When the liquid sample 9 is: pressed back and forth between thesecavities 4 it simulates a cleaning process, where the liquid sample 9,which e.g. contains enzymes, interact with the solid sample 10.

In order to enhance this interaction an optional vibration table 19 maybe arranged between the rollers 16 and 17 or at any other appropriateplace along the apparatus of FIG. 1.

After the liquid sample 9 and the solid sample 10 in each sealed systemof cavities have been allowed to interact as much as desired, the webwith the cavities 4 are passed under a last roller 18, as illustrated inFIG. 3 d. This last roller 18 is also profiled to present recesses andraised parts. The raised parts are aligned with the cavities containingthe solid samples 10. The raised parts of the last roller 18 press theliquid sample out of the cavity 4 containing the solid sample 10 andinto the neighbouring cavity 4 of the sealed system. Preferably the lastroller 18 is heated so as to weld the passage 15 shut, thereby isolatingthe liquid sample 9 from the solid sample 10. As can be seen from FIG. 3d, the raised parts of the roller 18 may have a shape to allow all ofthe liquid sample 9 to be pressed out of the cavity 4, in which thesolid sample 10 is located.

After the liquid samples 9 and the solid samples have been isolated fromeach other, the web is conveyed past an optical inspection station 20.This optical inspection station 20 measures the properties of interestof the solid samples 10, such as reflectivity or colour, and, ifdesired, of the liquid samples 9.

If the optical inspection of a solid sample 10 reveals that acorresponding liquid sample 9 has the desired properties it may readilyand unmistakably be identified by means of the aforementioned marking,e.g. the bar code. This is also the case even when the web is in a laststep of the process cut into segments 21, adapted in size for storageand other handling.

It should be noted that the description above relates only to apreferred embodiment of the present invention, and that numerousmodifications are possible within the scope of the claims. Thus, the barcode identifying the liquid samples 9 may be applied at any convenientstage, in particular in connection with the sealing of the cavities.Also the liquid samples 9 may be displaced in a direction along the webrather than across, as described above, or even both, if one of theother arrangements of the cavities illustrated in FIG. 4 is used.

1. A method for testing the interaction between at least one liquidsample and a respective solid sample said method comprising at least thesteps of providing adjacent first and second cavities, where said firstand second cavities are in mutual communication via at least onepassage, placing the solid sample in said first cavity, introducing theliquid sample in one of said first and second cavities, sealing at leastsaid first and second cavities from the exterior, so as to form a closedsystem of communicating cavities, bringing said liquid sample intocontact with the solid sample in said first cavity, transferringsubstantially all of said liquid sample to the second cavity after ithas been brought into contact with the solid sample, and testing thedesired properties of any one or both of said liquid sample or saidsolid sample.
 2. A method according to claim 1, wherein said liquidsample is repeatedly transferred between said first and second cavity,so as to enhance the interaction between said liquid sample and saidsolid sample.
 3. A method according to claim 2, wherein a plurality ofclosed systems of first and second cavities are provided.
 4. A methodaccording to claims 1, wherein said testing is performed withoutbreaking the sealing of said closed system
 5. A method according toclaim 4, wherein said testing comprises optical inspection of said solidsample in said first cavity after the transfer of substantially all ofsaid liquid sample to said second cavity.
 6. A method according to claim1, wherein the mutual communication between said first and said secondcavity is interrupted after said transfer of substantially all of saidliquid sample to said second cavity, so as to seal said first and secondcavities from each other.
 7. A method according to claim 1, wherein saidliquid is transferred between said cavities by means of rollers.
 8. Amethod according to claim 1 wherein the first and second cavities andthe at least one passage are repeatedly manufactured as recesses in afirst continuous web of flexible foil which are subsequently covered andsealed by a second continuous web of flexible foil.
 9. A methodaccording to claim 8 wherein said first continuous web is of athermoplastic material.
 10. A method according to claim 9 wherein saidsecond continuous web is of the same material as the first continuousweb.
 11. A method according to claim 9, wherein the first and secondwebs are joined by welding.
 12. A method according to claim 1, whereinsaid closed system of first and second cavities comprise at least onefurther cavity.
 13. A sealed system for the use in testing theinteraction between at least one liquid sample and a respective solidsample, said system comprising at least a first cavity, a second cavitya passage between said first cavity and said second cavity said solidsample and said liquid sample, and said first cavity, said second cavityand said passage all being provided between two flexible foils sealedtogether around said first cavity, said second cavity and said passageso as to form a closed system of communicating cavities.
 14. A sealedsystem according to claim 13 wherein said sealed system of cavitiescomprises at least one further cavity.
 15. A sealed system according toany of one of claims 13 or 14, wherein said flexible foils are weldedtogether.